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Genetics of aging bone

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Abstract

With aging, the skeleton experiences a number of changes, which include reductions in mass and changes in matrix composition, leading to fragility and ultimately an increase of fracture risk. A number of aspects of bone physiology are controlled by genetic factors, including peak bone mass, bone shape, and composition; however, forward genetic studies in humans have largely concentrated on clinically available measures such as bone mineral density (BMD). Forward genetic studies in rodents have also heavily focused on BMD; however, investigations of direct measures of bone strength, size, and shape have also been conducted. Overwhelmingly, these studies of the genetics of bone strength have identified loci that modulate strength via influencing bone size, and may not impact the matrix material properties of bone. Many of the rodent forward genetic studies lacked sufficient mapping resolution for candidate gene identification; however, newer studies using genetic mapping populations such as Advanced Intercrosses and the Collaborative Cross appear to have overcome this issue and show promise for future studies. The majority of the genetic mapping studies conducted to date have focused on younger animals and thus an understanding of the genetic control of age-related bone loss represents a key gap in knowledge.

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Acknowledgments

Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Numbers AR064941 (to D.R.) and AR060234 (to C.L.A.B.).

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, University of Connecticut Musculoskeletal Institute, University of Connecticut Health, Farmington, CT, 06030, USA

    Douglas J. Adams

  2. Center for Regenerative Medicine and Skeletal Development, Department of Reconstructive Sciences, Biomaterials and Skeletal Development, University of Connecticut Health, Farmington, CT, USA

    David W. Rowe

  3. Center for Musculoskeletal Research, Department of Orthopaedics and Rehabilitation, School of Medicine and Dentistry, University of Rochester, 601 Elmwood Ave, Box 665, Rochester, NY, 14624, USA

    Cheryl L. Ackert-Bicknell

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Adams, D.J., Rowe, D.W. & Ackert-Bicknell, C.L. Genetics of aging bone. Mamm Genome 27, 367–380 (2016). https://doi.org/10.1007/s00335-016-9650-y

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